BACKGROUND: Silybin, a major flavonoid extracted from the seeds of milk thistle, has a strong hepatoprotective but weak anti-hepatoma activity. Screening another natural ingredient and combining it with silybin is expected to improve the anti-hepatoma efficacy of silybin. OBJECTIVE: The objective of this study was to investigate the synergistic anti-hepatoma effect of resveratrol and silybin on HepG2 cells and H22 tumor-bearing mice in hepatocellular carcinoma (HCC) METHODS: Cell viability, scratch wound, clone formation, cell apoptosis, cell cycle, and western blot analysis of HepG2 cells were used to investigate the synergistic effects RESULTS: The combination of resveratrol (50 μg/mL) and silybin (100 μg/mL) significantly suppressed cell viability, whose combination index (CI) was 1.63 (>
1.15), indicating the best synergism. The combination exhibited the synergistic effect in blocking the migration and proliferative capacity of HepG2 cells in the measurement CONCLUSION: Resveratrol was found to exhibit synergistic anti-cancer effects with silybin on HepG2 cells and H22 tumor-bearing mice.